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Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.

Rizza RA - Diabetes (2010)

Bottom Line: Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present.I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia.While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. rizza.robert@mayo.edu

ABSTRACT
The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present. The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

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Rates of total body glucose disappearance and forearm glucose uptake observed in people with or without type 2 diabetes. Fifty grams of glucose was ingested at time zero (10).
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Figure 4: Rates of total body glucose disappearance and forearm glucose uptake observed in people with or without type 2 diabetes. Fifty grams of glucose was ingested at time zero (10).

Mentions: What about glucose disappearance? Was hyperglycemia due to lower rates in the diabetic subjects? As is evident from this side, the answer is no. As is evident from the upper panel of Fig. 4, if anything the rates of glucose disappearance were higher in the diabetic subjects than in the nondiabetic subjects both before and after glucose ingestion. Urinary glucose loss and muscle glucose uptake both contribute to glucose disappearance. Urinary glucose loss can be substantial when glucose concentrations exceed the renal glucose threshold as commonly happens after eating. To gain insight regarding muscle glucose uptake, Dr. Firth used the forearm catheterization method to measure forearm glucose uptake. As is evident from the lower panel of Fig. 4 in contrast to the higher rates of total body glucose disappearance, forearm glucose uptake did not differ in the diabetic and nondiabetic subjects (10). Taken together, these data indicate that people with type 2 diabetes have excessive rates of endogenous glucose production both before and after eating contributing to both fasting and postprandial hyperglycemia. In addition, while meal appearance and muscle glucose uptake did not differ in the diabetic and nondiabetic subjects, they were not appropriate for the prevailing glucose concentration.


Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.

Rizza RA - Diabetes (2010)

Rates of total body glucose disappearance and forearm glucose uptake observed in people with or without type 2 diabetes. Fifty grams of glucose was ingested at time zero (10).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963523&req=5

Figure 4: Rates of total body glucose disappearance and forearm glucose uptake observed in people with or without type 2 diabetes. Fifty grams of glucose was ingested at time zero (10).
Mentions: What about glucose disappearance? Was hyperglycemia due to lower rates in the diabetic subjects? As is evident from this side, the answer is no. As is evident from the upper panel of Fig. 4, if anything the rates of glucose disappearance were higher in the diabetic subjects than in the nondiabetic subjects both before and after glucose ingestion. Urinary glucose loss and muscle glucose uptake both contribute to glucose disappearance. Urinary glucose loss can be substantial when glucose concentrations exceed the renal glucose threshold as commonly happens after eating. To gain insight regarding muscle glucose uptake, Dr. Firth used the forearm catheterization method to measure forearm glucose uptake. As is evident from the lower panel of Fig. 4 in contrast to the higher rates of total body glucose disappearance, forearm glucose uptake did not differ in the diabetic and nondiabetic subjects (10). Taken together, these data indicate that people with type 2 diabetes have excessive rates of endogenous glucose production both before and after eating contributing to both fasting and postprandial hyperglycemia. In addition, while meal appearance and muscle glucose uptake did not differ in the diabetic and nondiabetic subjects, they were not appropriate for the prevailing glucose concentration.

Bottom Line: Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present.I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia.While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. rizza.robert@mayo.edu

ABSTRACT
The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present. The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

Show MeSH
Related in: MedlinePlus